Deletions in 16q24.2 are associated with autism spectrum disorder, intellectual disability and congenital renal malformation
Deletions in 16q24.2 are associated with autism spectrum disorder, intellectual disability and congenital renal malformation
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DOI：
10.1136/jmedgenet-2012-101288
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发表时间：
2013-03-01
影响因子：
4
通讯作者：
Rosenblum, Norman D.
中科院分区：
文献类型：
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作者：
Handrigan, Gregory Ryan;Chitayat, David;Rosenblum, Norman D.
随着基于阵列的比较基因组杂交（aCGH）和微阵列技术的广泛应用，拷贝数变异（CNV）对疾病的贡献已被强调。16q24.3中涉及ANKRD 11的连续体基因缺失与自闭症谱系障碍（ASD）和智力残疾（ID）相关，而影响FOXF 1的16q24.1缺失与先天性肾畸形、肺泡毛细血管发育不良和各种其他异常相关。目的探讨16q24.2基因缺失与先天性畸形的关系。方法35例16q24.2基因缺失的个体，其中16 q24.2基因缺失的个体16例，16 q24.2基因缺失的个体16例，16 q24.2基因缺失的个体16例，16 q24.2基因缺失的个体16例。在临床上以aCGH和/或SNP为特征，结果在35例16q24.2缺失中，有几例与FOXF 1和ANKRD 11的编码区紧密相邻或重叠，这两个基因以前与这种疾病有关。25例患者报告患有ASD/ID，3例发现双侧肾积水。与ASD/ID相关的缺失中有14个与FBXO 31和MAP 1 LC 3B的编码区重叠。这些相同的基因和其他两个，C16 orf 95和ZCCHC 14，也包括在该地区的最小重叠的三个缺失与hydronephilosis.Conclusions我们的数据突出16q24.2作为一个区域的利益ASD，ID和先天性肾畸形。这些疾病与影响C16 orf 95、ZCCHC 14、MAP 1 LC 3B和FBXO 31的缺失相关，尽管没有完全的突变。每个基因在发育和疾病中的功能需要进一步研究。
Background The contribution of copy-number variation (CNV) to disease has been highlighted with the widespread adoption of array-based comparative genomic hybridisation (aCGH) and microarray technology. Contiguous gene deletions involving ANKRD11 in 16q24.3 are associated with autism spectrum disorder (ASD) and intellectual disability (ID), while 16q24.1 deletions affecting FOXF1 are associated with congenital renal malformations, alveolar capillary dysplasia, and various other abnormalities. The disease associations of deletions in the intervening region, 16q24.2, have only been defined to a limited extent.Aim To determine whether deletions affecting 16q24.2 are correlated with congenital anomalies.Methods 35 individuals, each having a deletion in 16q24.2, were characterised clinically and by aCGH and/or SNP-genotyping microarray.Results Several of the 35 16q24.2 deletions identified here closely abut or overlap the coding regions of FOXF1 and ANKRD11, two genes that have been previously associated with the disease. 25 patients were reported to have ASD/ID, and three were found to have bilateral hydronephrosis. 14 of the deletions associated with ASD/ID overlap the coding regions of FBXO31 and MAP1LC3B. These same genes and two others, C16orf95 and ZCCHC14, are also included in the area of minimal overlap of the three deletions associated with hydronephrosis.Conclusions Our data highlight 16q24.2 as a region of interest for ASD, ID and congenital renal malformations. These conditions are associated, albeit without complete penetrance, with deletions affecting C16orf95, ZCCHC14, MAP1LC3B and FBXO31. The function of each gene in development and disease warrants further investigation.